Protoporphyrin IX (7,12-diethenyl 3,8,13,17-tetramethyl-21II,23II-porphine 2,18 dipropanoic acid) is the direct precursor of heme B (Fe-protoporphyrin IX), hemin (heme B with a chloride ligand), and hematin (hemin with a hydroxide ligand in place of the chloride). Heme is the prosthetic group for hemoproteins including hemoglobin and catalases, which are crucial for respiration and detoxification in humans and animals. The photosensitivity of protoporphyrin IX has been utilized in photodynamic therapy (PDT), a therapy against different forms of cancer. Protoporphyrin IX has been used as a therapeutic supplement for patients with infective hepatitis and chronic liver diseases. The biological heme synthesis pathway is very conservative among prokaryotes (e.g. bacteria) and eukaryotes (e.g., human). Ferrochelatase (EC 4.99.1.1) is the terminal enzyme in the heme biosynthesis pathway and catalyzes the insertion of Fe2+ into protoporphyrin IX. In the best-studied laboratory model bacterium Escherichia coli K12 strain, a hemH mutant is sensitive to visible light due to the accumulation of protoporphyrin IX. This is similar to the defect observed in human protoporphyria (Miyamoto et al. J Mol Biol. 1991, 219(3):393-398; Miyamoto et al. FEBS Lett. 1992, 310(3):246-248; Miyamoto et al. J Biochem. 1994, 115(3):545-551; Nakahigashi et al. Proc Natl Acad Sci USA. 1991, 88(23):10520-10524).
The price of protoporphyrin IX is about 36,000 $US/kg in the world market, and the products are usually extracted from livestock blood. It is known that such blood-based production processes are high cost, may cause contamination to the environment (e.g., due to use of large amounts of chemicals), and may present health risks to humans and animals (e.g., due to viruses and prions). The chemical synthesis of protoporphyrin has been proposed, but has not been commercially feasible due to high cost and possible contamination.